PD33-01 THE VIABILITY, METABOLISM AND VASCULARIZATION OF RENAL CELL CARCINOMA CELL LINES AND XENOGRAFTS CAN BE TARGETED THROUGH INHIBITION OF ENDOGENOUS HYDROGEN SULFIDE PRODUCTION

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2015PD33-01 THE VIABILITY, METABOLISM AND VASCULARIZATION OF RENAL CELL CARCINOMA CELL LINES AND XENOGRAFTS CAN BE TARGETED THROUGH INHIBITION OF ENDOGENOUS HYDROGEN SULFIDE PRODUCTION Eric Sonke, Megan Verrydt, Carl O. Postenka, Siddika Pardhan, Chantalle J. Willie, Clarisse Mazzola, Ian Lobb, Ann F. Chambers, Nicholas E. Power, Hon S. Leong, and Alp Sener Eric SonkeEric Sonke More articles by this author , Megan VerrydtMegan Verrydt More articles by this author , Carl O. PostenkaCarl O. Postenka More articles by this author , Siddika PardhanSiddika Pardhan More articles by this author , Chantalle J. WillieChantalle J. Willie More articles by this author , Clarisse MazzolaClarisse Mazzola More articles by this author , Ian LobbIan Lobb More articles by this author , Ann F. ChambersAnn F. Chambers More articles by this author , Nicholas E. PowerNicholas E. Power More articles by this author , Hon S. LeongHon S. Leong More articles by this author , and Alp SenerAlp Sener More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2099AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renal epithelial cells express enzymes involved in the detoxification of homocysteine. One of these enzymes, cystathionine β-synthase (CBS), produces the gasotransmitter hydrogen sulfide (H2S) in its metabolism of homocysteine and L-cysteine (LC). CBS upregulation and increased production of H2S has been reported to enhance cellular bioenergetics of various cancers through electron donation, and has also been shown to confer resistance to hypoxia through its cytoprotective and angiogenic properties. It is our hypothesis that H2S production is similarly enhanced in renal cell carcinoma (RCC) cell lines lacking functional Von Hippel-Lindau (VHL) tumour suppressor, contributing to cell survival and angiogenic potential. METHODS Changes in the viability and metabolism of three RCC cell lines (786-O, 769-P and Caki-1) and one non-malignant renal epithelial cell line (HK-2) were examined in vitro following normoxic (21% O2) and hypoxic (1% O2) treatment with the CBS inhibitor hydroxylamine (HA) and the CBS substrate LC. Similar treatments were administered to avian-xenografted tumours to assess changes in tumour vascularization of VHL-deficient (786-O, 769-P) and VHL-possessing (Caki-1, 786-O VHL+) RCC cell lines. RESULTS When endogenous H2S production was inhibited with HA, RCC cell lines displayed greater, significant (p < 0.05) declines in viability (Figure 1A) and metabolism (Figure 1B) compared to the non-malignant HK-2 cell line. Declines in hypoxic viability and metabolism of RCC cell lines could be attenuated when treated with LC (Figure 1). When xenografted in vivo, VHL-deficient, but not VHL-possessing, RCC tumours were observed to significantly (p < 0.05) decrease vascularization (Figure 2A) and size (Figure 2B) following treatment with HA. CONCLUSIONS These results report for the first time that inhibition of endogenous H2S production may be a valuable strategy in simultaneously targeting the growth and neovascularization of RCC tumours. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e709 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eric Sonke More articles by this author Megan Verrydt More articles by this author Carl O. Postenka More articles by this author Siddika Pardhan More articles by this author Chantalle J. Willie More articles by this author Clarisse Mazzola More articles by this author Ian Lobb More articles by this author Ann F. Chambers More articles by this author Nicholas E. Power More articles by this author Hon S. Leong More articles by this author Alp Sener More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...